Abstract:
BACKGROUND:While current chemotherapy has increased cure rates for children with acute lymphoblastic leukaemia (ALL), the largest number of relapsing patients are still stratified as medium risk (MR) at diagnosis (50-60%). This highlights an opportunity to develop improved relapse-prediction models for MR patients. We hypothesised that bone marrow from MR patients who eventually relapsed would regrow faster in a patient-derived xenograft (PDX) model after induction chemotherapy than samples from patients in long-term remission. METHODS:Diagnostic bone marrow aspirates from 30 paediatric MR-ALL patients (19 who relapsed, 11 who experienced remission) were inoculated into immune-deficient (NSG) mice and subsequently treated with either control or an induction-type regimen of vincristine, dexamethasone, and L-asparaginase (VXL). Engraftment was monitored by enumeration of the proportion of human CD45+ cells (%huCD45+) in the murine peripheral blood, and events were defined a priori as the time to reach 1% huCD45+, 25% huCD45+ (TT25%) or clinical manifestations of leukaemia (TTL). RESULTS:The TT25% value significantly predicted MR patient relapse. Mutational profiles of PDXs matched their tumours of origin, with a clonal shift towards relapse observed in one set of VXL-treated PDXs. CONCLUSIONS:In conclusion, establishing PDXs at diagnosis and subsequently applying chemotherapy has the potential to improve relapse prediction in paediatric MR-ALL.
journal_name
Br J Cancerjournal_title
British journal of cancerauthors
Alruwetei AM,Bendak K,Yadav BD,Carol H,Evans K,Mayoh C,Sutton R,Marshall GM,Lock RBdoi
10.1038/s41416-020-0933-4subject
Has Abstractpub_date
2020-09-01 00:00:00pages
742-751issue
5eissn
0007-0920issn
1532-1827pii
10.1038/s41416-020-0933-4journal_volume
123pub_type
杂志文章abstract::Photodynamic diagnosis and therapy have emerged as a promising tool in oncology. Using the visible fluorescence from photosensitisers excited by light, clinicians can both identify and treat tumour cells in situ. Protoporphyrin IX, produced in the penultimate step of the haem synthesis pathway, is a naturally occurrin...
journal_title:British journal of cancer
pub_type: 杂志文章,评审
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journal_title:British journal of cancer
pub_type: 杂志文章
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pub_type: 杂志文章,随机对照试验
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journal_title:British journal of cancer
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pub_type: 共识发展会议,杂志文章,评审
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pub_type: 临床试验,杂志文章
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journal_title:British journal of cancer
pub_type: 杂志文章
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abstract:BACKGROUND:Stromal-tumour interactions facilitate pancreatic cancer (PC) progression. The hepatocyte growth factor (HGF)/c-MET pathway is upregulated in PC and mediates the interaction between cancer cells and stromal pancreatic stellate cells (PSCs). This study assessed the effect of HGF/c-MET inhibition plus gemcitab...
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pub_type: 杂志文章,随机对照试验
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